A5083080792- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Influenza Virus Research Studies
- interferon and immune responses
- Animal Disease Management and Epidemiology
- RNA Research and Splicing
- Herpesvirus Infections and Treatments
- RNA modifications and cancer
- Immune Response and Inflammation
- Microbial infections and disease research
- COVID-19 Impact on Reproduction
- COVID-19 epidemiological studies
- Radiopharmaceutical Chemistry and Applications
- Global Maternal and Child Health
- Cytokine Signaling Pathways and Interactions
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Mycobacterium research and diagnosis
- Cancer, Hypoxia, and Metabolism
International Institute of Molecular and Cell Biology
2021-2024
University of Saskatchewan
2018-2022
Ghent University
2014-2020
Abstract The E3 ubiquitin ligase TRIM25 is a key factor in the innate immune response to RNA viruses. has been shown play role retinoic-acid-inducible gene-1 (RIG-I) pathway, which triggers expression of type 1 interferons upon viral infection. We and others have that an RNA-binding protein; however, viruses unclear. Here, we demonstrate influenza A virus (IAV A/PR/8/34_NS1(R38A/K41A)) infection inhibited by TRIM25. Surprisingly, previously identified deficient mutant TRIM25ΔRBD TRIM25ΔRING,...
Studies in mice showed that African Zika virus (ZIKV) strains cause more damage embryos. These studies, however, were limited to the mouse-adapted MR766 strain or infection at early gestation. Here, we compared of Asian and fetal pig model midgestation. Both caused infection. ZIKV was detected placenta, amniotic membrane, fluid, blood, brain. The produced vigorous utero as represented by efficient transmission between siblings, higher viral loads organs membranes. Infection with both...
Abstract Background The NCI MATCH trial has shown that only 1 out of 4 patients carry actionable driver mutations.1 Hence, functional precision medicine leverages ex-vivo tumor models complementing genomic testing is experiencing a renaissance.2 Because most late-stage cancers tend to be heterogeneous and some anticancer drugs affect viability while others inhibit proliferation, we have developed novel multiplexed approach for simultaneously assessing cellular proliferation patient cancer...
Abstract Background Tumor heterogeneity is a key driver of drug resistance in late-stage cancers and metastases are often thought to exhibit distinct sensitivity profiles compared primary tumors. We developed live 3D microtumor functional profiling model that preserves the tumor microenvironment provides clinically relevant results within 7 10 days. While this reflects patient’s biopsy, it remains uncertain whether changes mutation may translate into meaningful differences resistance....
In this study, the pathogenic behavior of PRRSV 13V091 and 13V117, isolated in 2013 from two different Belgian farms with enzootic respiratory problems shortly after weaning nursery, were compared strain 07V063 2007. Full-length genome sequencing was performed to identify their origin. Twelve weeks-old pigs inoculated intranasally (IN) 13V091, 13V117 or (9 pigs/group). At 10 days post inoculation (dpi), 4 animals each group euthanized tissues collected for pathology, virological serological...
In the present study, replication kinetics of nephropathogenic (B1648) and respiratory (Massachusetts-M41) IBV strains were compared in vitro mucosa explants blood monocytes (KUL01+ cells), vivo chickens to understand why some have a kidney tropism. B1648 was replicating somewhat better than M41 epithelium used more KUL01+ cells penetrate deeper layers tract. productively monocytic contrast with M41. inoculated animals, 102.7–6.8 viral RNA copies/100 mg detected tracheal secretions at 2, 4,...
Experimental increase of CpG dinucleotides in an RNA virus genome impairs infection providing a promising approach for vaccine development. While recoding is emerging and approach, little known about phenotypes caused by recoded viruses vivo. For example, phenotypes, immunogenicity, protective efficacy induced CpG-recoded different age groups were not studied yet. This important, because attenuation may depend on the population-based expression cellular components targeting viral...
The emergence of multiple novel lineages H1 and H3 influenza A viruses in swine has confounded control by inactivated vaccines. Because substantial genetic geographic heterogeneity among circulating viruses, one vaccine strain per subtype cannot be efficacious against all the current lineages. We have performed vaccination-challenge studies pigs to examine whether priming booster vaccinations with antigenically distinct H3N2 could broaden antibody responses protection. prepared monovalent...
We studied whether cytosine phosphate-guanine (CpG) recoding in a viral genome may provide oncolytic candidates with reduced infection kinetics nonmalignant brain cells, but high virulence glioblastoma stem cells (GSCs). As model, we used well-characterized CpG-recoded Zika virus vaccine that previously showed genetic stability and safety animal models. In vitro, one of the variants had infectivity activity GSCs as represented by cell proliferation. The recoded also efficiently replicated...
Abstract The zinc finger antiviral protein 1 (ZAP) has broad activity. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN response. In a previous study, Zika virus was identified as ZAP-resistant and not sensitive to Here, we found that associated with the inhibition of in Vero cells, absence robust system because cells are deficient for IFN-alpha -beta. Also, quantitative RNA-seq data indicated endogenous altered global gene expression both steady state during...
Cellular entry mediators define whether the cell is permissive to PRRSV infection. Porcine sialoadhesin (pSn, Siglec-1) and CD163 are main facilitating infection of porcine macrophages by PRRSV. Recently, Siglec-10 was demonstrated be an alternative receptor for To examine if virulence pathogenicity strains could correlated with use different Siglecs, a PK15 line recombinantly expressing Siglec-1 (PK15S1–CD163) (PK15S10–CD163) were used compare virus replication 7 genotype 1 subtype (G1s1),...
Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical not associated with evident birth defects. Potentially detrimental life-long health outcomes asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae provide valuable information. To induce infection, we inoculated selected porcine fetuses at mid-stage development. Inoculation resulted...
Porcine circovirus type 2 (PCV2) is associated with various diseases which are designated as PCV2-associated (PCVADs). Their severity varies among breeds. In the diseased pigs, virus present in monocytes, without replication or full degradation. PCV2 entry and viral outcome primary porcine monocytes role of genetic susceptibility have not been studied. Here, uptake trafficking were analyzed compared purebreds Piétrain, Landrace Large White hybrid Piétrain × Topigs20. Viral capsids rapidly...
The Meat Animal Research Center-145 (MARC-145) cell line has been proven to be valuable for viral attenuation regarding vaccine development and production. Cell-adaptation is necessary the efficient replication of porcine reproductive respiratory syndrome virus (PRRSV) in these cells. Multiple sequence analysis revealed consistent amino acid substitutions GP2a (V88F, M94I, F95L) MARC-145 cell-adapted strains. To investigate putative effect substitutions, mutations at either position 88, 94,...
The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA inducing abortion in sows disease young pigs, is a leading infectious cause of economic losses the swine industry. Modified live vaccines (MLVs) help controlling disease, but their efficacy often compromised by high genetic diversity circulating viruses, to vaccine escape variants field. In this study, we hypothesized that DNA prime with naked plasmids encoding PRRSV antigens containing conserved T-cell epitopes may...
The Zika virus 2015 epidemic showed an unusual phenotype for human flaviviruses, specifically fetal infection. We previously that in utero inoculation with the Asian isolated from sample causes persistent infection porcine fetuses. Here, we characterized evolution of brain and placenta. Interestingly, acquired generic African lineage K101R (A408G) R1609 K (G4932A) mutations during Both were nonsynonymous had a high frequency nearly 100% brain. Then, synthetically generated wild-type variant...
The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows respiratory illnesses growing pigs is considered as one of the main pathogenic agents responsible for economic losses porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection heterologous viral variants. With goal to induce broad cross-protective immunity, we generated DNA encoding B...
Increasing the number of CpG dinucleotides in RNA viral genomes, while preserving original amino acid composition, leads to impaired infection which does not cause disease. Beneficially, evokes antiviral host immune responses providing a cutting-edge vaccine approach. For example, we previously showed that CpG-enriched Zika virus variants attenuated phenotypes and protect against lethal challenge mice. While recoding is an emerging promising approach, little known about caused by recoded...
The zinc finger antiviral protein 1 (ZAP) has broad activity. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN response. In a previous study, Zika virus was identified as ZAP-resistant and not sensitive to Here, we found that associated with the inhibition of in Vero cells, absence robust system because cells are deficient for IFN-alpha -beta. Also, quantitative RNA-seq data indicated endogenous altered global gene expression both steady state during infection....
Abstract In vitro transcription (IVT) is a technology of vital importance that facilitated the production mRNA therapeutics and drove numerous breakthroughs in RNA biology. T7 polymerase-produced RNAs can begin with either 5′-triphosphate guanosine (5′-pppG) or adenosine (5′-pppA), generating potential agonists for RIG-I/type I interferon response. While it established IVT yield highly immunogenic double-stranded (dsRNA) via promoterless transcription, specific contribution initiating...